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Hyaluronan depletion improved intratumor pO2 and sensitized tumor to radiation therapy in pancreatic cancer model mouse.
Yu Saida1, Tomohiro Seki2, Shun Kishimoto1, Yasunori Otowa1, Kota Yamashita1, Kazutoshi Yamamoto1, Nallathamby Devasahayam1, Jeffrey R. Brender1, and Murali C. Krishna1
1Radiation Biology Branch, National Cancer Institute, Bethesda, MD, United States, 2Laboratory of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama, Japan
Multimodal-molecular imaging showed improved oxygenation, increased blood volume, and decreased lactate-to-pyruvate ratio in tumors in response to PEGPH20 treatment. PEGPH20 could enhance the effect of radiotherapy.

Fig. 3 HP [1-13C] Pyruvate MRI showed decreased Lac/Pyr ratio after PEGPH20 treatment.

HP [1-13C] Pyruvate MRI was performed in BxPC3-HAS3 tumor bearing mice treated with control buffer or PEGPH20 before and after treatment. A, Representative kinetics of [1-13C] pyruvate and [1-13C] lactate and its anatomical 1H image. B, Lac/Pyr ratio of each tumor are shown by treatment group. Individual values are shown. C, Lac/Pyr ratio change from the baseline (pre-treatment) of each group.

Fig. 1 EPR imaging showed increased pO2 after PEGPH20 treatment.

EPR imaging was performed in BxPC3-HAS3 tumor bearing mice treated with control buffer or PEGPH20 before and after treatment. A, Representative oxygen map obtained by EPR imaging and T2-weighted anatomical image. B, Histograms of pO2 distribution within the tumor of each group. C, The mean pO2 of each tumor shown by treatment group. D, pO2 change (%) from the baseline (pre-treatment) of each group.